EP2540341B1 - Cardiac stimulator for delivery of cardiac contractility modulation therapy - Google Patents

Description

The invention relates to a cardiac stimulator for delivery of cardiac contractility modulation therapy.

Implantable cardiac stimulators in the form of cardiac pacemakers or cardioverters / defibrillators are generally known. Such cardiac stimulators are typically connected to electrode leads that have stimulation and optionally additional defibrillation electrodes in a chamber of a heart or in close proximity. Via a stimulation electrode, a pacemaker can deliver an electrical stimulation pulse to the muscle tissue of a heart chamber so as to cause a stimulated contraction of the ventricle, as long as the stimulation pulse is of sufficient intensity and the myocardial tissue (myocardium) is not in a refractory phase. Such a stimulated contraction of a heart chamber is referred to in this description as a stimulated event. If there is a natural contraction of the heart chamber, this is referred to in the context of this description as a private action or as a natural or intrinsic event. A contraction of, for example, the right atrium of a heart is referred to as an atrial event, which may be, for example, a natural atrial event or, in the case of an atrial pacemaker, also a stimulated atrial event. In the same way, natural (intrinsic) and stimulated left ventricular and right ventricular events can be distinguished.

A local arousal of the myocardium spreads from the excitation site via stimulation in the myocardium and leads to a depolarization of the muscle cells and thus to a contraction of the myocardium. After a short time a repolarization of the muscle cells occurs and thus a relaxation of the myocardium. During the phase of depolarization the cardiac muscle cells are insensitive to arousal, ie refractory. This time is called the refractory period. The associated with the depolarization and depolarization electrical potentials can be perceived and their time course - referred to as electrocardiogram - evaluated.

In healthy people, the respective heart rhythm is determined by the sinus node controlled by the autonomic nervous system. This stimulates the right atrium of a human heart by stimulation, and continues via the AV node to the (right) ventricle of the heart. A natural heart rhythm emanating from the sinus node is therefore also called sinus rhythm and leads to natural contractions of the respective heart chamber, which can be detected as natural (intrinsic) events.

The detection of such natural (intrinsic) events is carried out by deriving the electrical potentials of the myocardium of the respective heart chamber by means of sensing electrodes, which are part of a corresponding electrode line. In this case, the sensing electrodes can simultaneously be the stimulation electrodes and used alternately as stimulation electrodes and as sensing electrodes. Typically, for the sensing-i.e. the perception of intrinsic events - a Sensingelektrodenpaar provided, which is formed by two adjacent electrodes, namely a tip electrode (tip electrode) and a ring electrode, of which the tip electrode also serves as a stimulation electrode. In this way, a bipolar derivative of an intracardiac electrocardiogram (IEGM) takes place. The sensing and stimulation in the ventricle is performed by means of a ventricular lead and the stimulation and sensing in the atrium (in the right atrium) with an atrial lead connected separately to the respective heart stimulator. In addition, a left ventricular electrode lead can also be provided, which typically projects beyond the coronary sinus and a lateral vein branching off from it into the vicinity of the left ventricle and may have a small-area stimulation and / or sensing electrode there.

The sensing electrodes are connected in operation of the heart stimulator with corresponding sensing units, which are designed to evaluate a respective via a sensing electrode (or a pair of sensing electrodes) recorded electrocardiogram and in particular to detect intrinsic atrial or ventricular events, ie natural atrial or ventricular contractions. This is done, for example, by threshold value comparison, ie an intrinsic event is detected when a respective intracardiac electrocardiogram exceeds a suitably predetermined threshold value.

From the frequency with which atrial or ventricular events follow one another, the respective intrinsic atrial heart rate (atrial frequency) or ventricular heart rate (ventricular frequency) can be derived and thus, for example, tachycardias can be detected.

The detection of natural events in known demand pacemakers also serves to suppress (inhibit) the delivery of pacing pulses to a corresponding ventricle if the natural event is detected in a time window prior to the scheduled delivery of a pacing pulse to that ventricle. In rate-adaptive cardiac pacemakers, the timing of delivery of a respective stimulation pulse is scheduled in response to a particular stimulation rate that is intended to meet the physiological needs of a patient, that is, for example, greater in case of greater effort. For this purpose, a heart stimulator may be equipped with one or more activity sensors, which may be, for example, a CLS sensor described in more detail below.

The natural effect of the autonomic nervous system on the heart rate (heart rate), which is modeled by a rate-adaptive heart stimulator, is called chronotropy.

In addition to chronotropy, cardiac output is also determined by its contractility, the influence of which is termed inotropy.

To determine the contractility of a heart, it is known to place in an enclosure of a cardiac stimulator (eg, an implantable cardiac pacemaker) an impedance or conductivity measurement unit configured to generate a unipolar or bipolar impedance or conductivity waveform. For this purpose, a plurality of impedance or conductivity values or a corresponding impedance or conductivity profile are measured during at least one cardiac cycle. This is done either unipolar by measuring between a neutral electrode and a measuring electrode or between two measuring electrodes. In addition, an evaluation unit is arranged in the housing, which serves for evaluating the impedance or conductivity profile and for deriving a contractility value from the impedance or conductivity profile. Electro-therapy devices, which can detect the contractility of a heart, offer the possibility of adapting a therapy to be delivered by the electrotherapy device to the respective contractility state of the patient's heart.

• eine direkte Steuerung durch das autonome Nervensystem (ANS),
• den sogenannten Starling-Mechanismus, und
• den sogenannten Bowditch-Effekt (Kraft-Frequenzkopplung).

As indicated, contractility describes an inotropic condition of a heart. Contractility affects the strength and speed of myocardial contraction. Contractility is controlled by three mechanisms:

• direct control by the autonomic nervous system (ANS),
• the so-called Starling mechanism, and
• the so-called Bowditch effect (force-frequency coupling).

The main mechanism, the control of circulatory regulation by the autonomic nervous system, increases contractility and heart rate when there is an increased metabolic demand, such as physical or physical exertion, to ensure proper blood supply. In healthy humans, the inotropy of the heart thus causes an increase in contractility with increased physiological needs.

In patients with chronic heart failure (HF), myocardial contractility decreases to a low level and interventricular synchronization is worsened. This is accompanied by a low ejection fraction (EF), low quality of life and high mortality. HF is common in the population. More recently, HF patients are being treated with resynchronization therapy devices, such as 3-chamber pacemakers or defibrillators. The aim of such a pacemaker therapy is to synchronize the two ventricles of a heart by biventricular stimulation to improve the timing of the heart chambers and thus the cardiac output. Such a therapy will also known as Cardiac Resynchronization Therapy (CRT). Cardiac Resynchronization Therapy (CRT) is well known and is offered, for example, by the Biotronik CRT-D Implants (Lumax HF-T).

Since the contractility of the heart is physiologically controlled by the autonomic nervous system, the detection of contractility can also be used to set a physiologically adequate stimulation rate in rate-adaptive cardiac pacemakers. This kind of stimulation rate control, which has already been mentioned earlier, is also known as Closed Loop Stimulation (CLS).

For the CLS, the intracardiac impedance curve is measured after the onset of ventricular contraction. This measurement is performed on both intrinsic and stimulated events. There is a direct dependence between the right ventricular impedance curve and the contraction dynamics. The contraction dynamics in turn is a parameter for the stimulation of the heart by the sympatheticus.

The closed loop stimulation serves as mentioned the stimulation rate control in a rate-adaptive pacemaker.

Cardiac Contractility Modulation (CCM) is known to increase cardiac contractility.

For example, Impulse Dynamics offers a so-called OPTIMIZER system for CCM therapy. This system includes a stimulation pulse generator connected to 3 electrodes, one of which is located in the atrium during operation and 2 in the right ventricular septum of the patient. The therapy is based on the delivery of biphasic stimulation pulses with an amplitude of 7-10V and a total pulse duration of ~20ms into the absolute refractory period of the ventricle with the aim to increase the contractility. The therapy is given for certain time units of the day (eg alternately 1h on, 1h off).

The principle of cardiac contractility modulation therapy is among others in US 6,317,631 B1 described.

The effect of CCM therapy is based - it is currently thought - in a modification of the cellular calcium ion exchange and thus leads to an increased contractile force, which should also result in a present atrial fibrillation therapeutic benefit. Although this has not yet been clinically proven, it is pathophysiologically understandable.

US 2010/0069977 A1 . US 2010/0069980 A1 . US 2010/0069984 A1 . US 2010/0069985 A1 describe methods to deliver CCM stimulation as needed. Here is the use of physiological sensors, kidney or heart function sensors, electrolyte sensors, serum sensors (eg creatinine), neurosensors (vagus, sympathetic), adverse event detectors, Worsening Heart Failure sensors, MRI sensors, activity sensors, sleep apnea sensors, ischemia sensors , Sensors for the metabolic demand and infarct sensors and cardiac rhythm-dependent CCM controls are generally described. In the cited prior art is also a shutdown of CCM therapy in detected atrial fibrillation or atrial arrhythmias (see US 2010/0069977 20A and 0332). There is also a general focus on the possible combination of CCM with other forms of stimulation and electrotherapy, such as CRT, ICD and neurostimulation.

• wenigstens eine Stimulationseinheit, die mit einer oder mehreren Stimulationselektroden verbunden oder zu verbinden ist und ausgebildet ist, auf ein entsprechendes Ansteuersignal hin Stimulationsimpulse zur Abgabe über wenigstens eine Stimulationselektrode zu generieren, sowie
• mit einer Herzrhythmuserfassungseinheit, die ausgebildet ist, wenigstens einen atrialen Herzrhythmus zu erfassen und
• eine Steuereinheit, die mit der Stimulationseinheit und der Herzrhythmuserfassungseinheit verbunden und ausgebildet ist, eine Stimulationsimpulsabgabe über die Stimulationseinheit derart zu steuern, dass der Herzstimulator überschwellige Stimulationsimpulse zur Anregung einer Kontraktion einer Herzkammer und unterschwellige Stimulationsimpulse für eine kardiale Kontraktionsmodulationstherapie abgeben kann.

A device according to the preamble of claim 1 is of WO 2007/029254 known. The invention has for its object to provide an improved heart stimulator. According to the invention this object is achieved by a heart stimulator. This includes

• at least one stimulation unit which is connected or connectable to one or more stimulation electrodes and is designed to generate stimulation pulses for delivery via at least one stimulation electrode in response to a corresponding actuation signal, and
• with a cardiac rhythm detection unit which is designed to detect at least one atrial cardiac rhythm and
• a control unit coupled to the stimulation unit and the cardiac rhythm sensing unit and configured to control a stimulation pulse delivery via the stimulation unit such that the cardiac stimulator can deliver suprathreshold stimulation pulses to induce contraction of a cardiac chamber and subliminal stimulation pulses for cardiac contraction modulation therapy.

According to the invention, the control unit is configured, in response to detection of an atrial arrhythmia by the cardiac rhythm sensing unit, to drive the stimulation unit to generate and deliver subthreshold stimulation pulses for cardiac contractility modulation therapy in cardiac contractility modulation therapy, and in response to sensing a sinus rhythm Cardiac arrhythmia detection unit to control the stimulation unit so that it can deliver at least when needed suprathreshold stimulation pulses to stimulate a contraction of a heart chamber, but no subliminal stimulation pulses for a cardiac contraction modulation therapy.

In other words, the object is achieved by a combined cardiac stimulator for CRT stimulation and CCM stimulation, which is connected to a rhythm weighting unit, which can either detect an existing sinus rhythm or classify an atrial arrhythmia and which has an additional therapy selection unit, the therapy selection unit Selecting either CRT therapy or CCM therapy based on the classification of the atrial rhythm such that CRT therapy is preferred in sinus rhythm and CCM therapy is delivered in atrial arrhythmia.

This cardiac stimulator is thus a device for the combined use of cardiac resynchronization therapy (CRT) and cardiac contractility modulation (CCM) in an electronic implant.

The heart stimulator is able to select the respective form of therapy in such a way that in each case that therapy is activated, which at the moment has the largest therapy deficit for represents the patient. In this way, the cardiac stimulator is able to combine Cardiac Contractility Modulation (CCM) and Cardiac Resynchronization Therapy (CRT) to deliver maximum expected clinical benefit to the patient, using their respective therapy whenever needed if this represents the superior treatment concept.

The heart stimulator according to the invention offers the advantage that, depending on the rhythm status of a heart failure patient, the most effective therapy is automatically selected and thus an increase in therapy efficiency is achieved. The benefits of CCM therapy and CRT are combined in one device.

The invention includes the insight that US 2010/0069977 A1 . US 2010/0069980 A1 . US 2010/0069984 A1 . US 2010/0069985 A1 Although describe a shutdown of CCM therapy in a detected atrial fibrillation or atrial arrhythmias. However, this is not the reason for the CCM shutdown. It may be suspected that CCM therapy may not be properly synchronized in atrial arrhythmias. However, this is not traceable to a CCM timing linked to the ventricular event.

However, since CCM therapy is currently preferred as a treatment option for so-called CRT non-responders and atrial arrhythmia is one of the known causes of CRT non-response, the invention recognizes here a promising approach, the CCM therapy just in the presence of To activate atrial arrhythmias.

US 2010/0069977 A1 . US 2010/0069980 A1 . US 2010/0069984 A1 . US 2010/0069985 A1 While they also describe the possible combination of CCM and CRT stimulation in a device, they do not specifically address the possible switches between CCM and CRT stimulation. Only a different stimulation threshold of CRT stimulation and CCM is considered.

The heart stimulator presented here is based on the assumption that, in the case of sinus rhythm, the CRT stimulation of a CCM therapy is clear with regard to the therapeutic benefit is superior. However, in atrial arrhythmias, particularly atrial fibrillation, CCM therapy is more effective than CRT pacing (at least in selected patients). The background is that the CRT stimulation causes a mechanical resynchronization of the heart, whereby the benefit was only proven if an adequate atrio-ventricular synchronization is present in addition to the interventricular resynchronization. Otherwise, the positive effect of CRT stimulation is more than offset by the lack of AV synchronization.

Preferably, the cardiac rhythm sensing unit comprises an atrial rhythm estimation unit connected to an atrial electrode configured to be placed in the right atrium of a heart.

Preferably, the arrhythmia detection unit and possibly its atrial rhythm assessment unit is designed to evaluate the frequency and stability of a ventricular rhythm in order to diagnose atrial fibrillation.

Preferably, the cardiac stimulator is an implantable cardioverter / defibrillator (ICD) and / or a biventricular pacemaker (CRT-D) and / or a neurostimulator.

Preferably, the control unit is configured such that cardiac contractility modulation therapy (CCM therapy) is additionally controlled by another sensor (activity, metabolic demand, closed loop stimulation (CLS), ventricular potential, renal function sensor, pulmonary function sensor, cardiac function sensor, electrolyte sensor, neurosensor / vagus / Sympathetic, adverse event sensor, heart failure sensor, sleep apnea sensor, ischemia sensor, infarct sensor, etc.).

Preferably, the heart stimulator is also an implantable cardioverter for the electrical conversion of atrial fibrillation, wherein the controller is configured so that a cardioversion attempt of the atrial fibrillation always precedes a defined phase of a CCM therapy to improve the cardioversion success. Such a preferred heart stimulator serves the purpose of initially normalizing the left atrial pressure conditions by the CCM therapy before cardioversion takes place.

To achieve the object, a method for the therapy of a heart is proposed in which either a cardiac contractility modulation therapy (CCM) or a cardiac resynchronization therapy (CRT) is delivered and the cardiac contractility modulation therapy is delivered when an atrial arrhythmia is present and then the cardiac resynchronization therapy delivered if there is no atrial arrhythmia.

A variant of the method relates to an operating method for a corresponding cardiac stimulator also for non-therapeutic purposes.

Fig. 1

einen Herzstimulator als CRT-CCM-Stimulator;

Fig. 2

ein Blockschaltbild wesentlicher Komponenten des Herzstimulators; und

Fig. 3

ein Ablaufdiagramm für die Therapieauswahl.

The invention will now be explained in more detail by means of exemplary embodiments with reference to the figures. From these shows:

Fig. 1

a heart stimulator as a CRT-CCM stimulator;

Fig. 2

a block diagram of essential components of the heart stimulator; and

Fig. 3

a flowchart for the therapy selection.

In the Fig. 1 is shown as an implementation example, a three-chamber ICD system with switchable CRT-CCM function. The heart stimulator (pulse generator or simply generator) 100 is connected to a plurality of implantable electrode lines 110, 112, 114 and 116. The generator 100 has a housing 102, which is in the example of metal and therefore electrically conductive and hermetically sealed. In the housing 102 electronic and electrical components of the generator 100 such as a battery, control electronics, stimulation pulse generators, perception units (also referred to as sensing units) with appropriate amplifier and filter electronics housed. These components are detachably connected to the electrode lines 110, 112, 114 and 116 via electrical plug-in connections in a connection housing 104 (also referred to as header) of the generator 100.

For right ventricular sensing and pacing, the right ventricular electrode lead 110 includes a right ventricular tip electrode 121 and a right ventricular ring electrode 122 at the distal end. The right ventricular tip electrode 121 delivers the right ventricular pacing pulses for biventricular CRT pacing. For defibrillation shock delivery, a distal shock coil 123 and optionally also a proximal shock coil 124 are attached to this right ventricular electrode lead 110. The counter electrode forms the generator housing 100 here.

The right atrial electrode lead 116 has a bipolar sensing and pacing pole (with a right atrial tip electrode 131 and a right atrial ring electrode 132) at its distal end and serves to sense the atrial rhythm and, if necessary, atrial pacing.

For CCM stimulation-that is to say for cardiac contractility modulation therapy-one or more right-ventricular septal electrode lines 112 are provided, which emit the CCM pulses via a tip electrode 141 and ring electrode 142 to the ventricular septum, respectively.

In addition, the system also includes a left ventricular or CS (coronary sinus) electrode lead 114 for indicating left ventricular pacing pulses to the CRT via a left ventricular tip electrode 151 and left ventricular ring electrode 152. For more effective defibrillation / cardioversion, a left ventricular shock coil 153 is optionally available.

Communication with external programming and control and communication devices 160 is via a wireless bidirectional telemetry unit.

In the Fig. 2 a schematic block diagram of a combined CRT CCMStimulators is shown. This comprises at least the following components: generator 200; right atrial electrode 210, connected to an atrial sense and stimulation unit 220 for classifying the atrial rhythm and on-demand atrial pacing; right and left ventricular electrode terminals 230 connected to a biventricular sensing and stimulating unit 240 for sensing and classifying the ventricular rhythm and biventricular CRT pacing and one or more CCM electrodes 250 connected to a CCM pacing unit 260, the atrial sensing and pacing unit 220, the biventricular sensing and pacing units Stimulation unit 240 and the CCM stimulation unit 260 are connected to a control unit 270. The control unit 270 includes a therapy selection unit 271. This therapy selection unit 271 activates either the biventricular stimulation unit 240 or the CCM stimulation unit 260 according to the classified atrial rhythm.

The biventricular sensing and pacing unit 240 includes a per se known ventricular pacing unit 241 and sensing unit 242. In addition, the biventricular sensing and pacing unit 240 includes a ventricular rhythm score unit 243.

The atrial sensing and stimulating unit 220 is configured to classify the atrial rhythm and on-demand atrial pacing of the atrium and includes the per se known atrial pacing unit 221 and sensing unit 222. In addition, the atrial pacing and pacing unit 220 includes an atrial rhythm score unit 223 having a classification performs the atrial rhythm in a conventional manner and, for example by analyzing the atrial heart rate is able to recognize atrial fibrillation and to distinguish it from non-pathological atrial rhythms. The output of the atrial rhythm evaluation unit 223 is supplied to the therapy selection unit 271.

A hemodynamic or activity sensor 280 provides an output during operation which reflects the metabolic demand of a patient and which may also be evaluated by the therapy selection unit 271.

Fig. 3 shows the operation of the therapy selection unit 271 based on a flowchart for the therapy selection. If the atrial rhythm assessment unit 223 detects atrial fibrillation or atrial arrhythmia (Afib), the therapy selection unit switches 271 CCM pacing on and biventricular pacing off. If there is no atrial fibrillation, the therapy selection unit 271 turns off CCM pacing and bi-ventricular pacing.

Claims (6)

1. A cardiac stimulator

   - comprising at least one stimulation unit, which is connected or connectable to one or more stimulation electrodes and which is configured to generate stimulation pulses to be delivered via at least one stimulation electrode in response to a relevant trigger signal,

   - comprising a cardiac rhythm detection unit, which is configured to detect at least one atrial cardiac rhythm, and

   - comprising a control unit, which is connected to the stimulation unit and the cardiac rhythm detection unit and which is configured to control a delivery of a stimulation pulse via the stimulation unit such that the cardiac stimulator can deliver above-threshold stimulation pulses to stimulate contraction of a ventricle, and sub-threshold stimulation pulses for cardiac contraction modulation therapy,

   wherein
   the control unit is configured tocontrol the stimulation unit in response to detection of atrial arrhythmia by the cardiac rhythm detection unit, such that said stimulation unit can deliver sub-threshold stimulation pulses for cardiac contraction modulation therapy,
   characterised in that
   the control unit is also configured to control the stimulation unit in response to detection of a sinus rhythm by the cardiac rhythm detection unit, such that said stimulation unit can deliver above-threshold stimulation pulses to stimulate a contraction of a ventricle, but not sub-threshold pulses for cardiac contraction modulation therapy.
2. The cardiac stimulator according to claim 1, characterised in that the cardiac rhythm detection unit comprises an atrial rhythm evaluation unit, which is connected or connectable to an atrial electrode configured for placement in the right atrium of a heart.
3. The cardiac stimulator according to claim 1 or 2, characterised in that the cardiac rhythm detection unit and, where applicable, an atrial rhythm evaluation unit assigned thereto is/are configured to evaluate the frequency and stability of a ventricular rhythm in order to diagnose atrial fibrillation.
4. The cardiac stimulator according to any one of claims 1 to 3, characterised in that the cardiac stimulator is an implantable cardioverter/defibrillator (ICD) and/or a biventricular cardiac pacemaker (CRT-D) and/or a neurostimulator.
5. The cardiac stimulator according to claim 4, characterised in that the cardiac stimulator is also an implantable cardioverter for electrical conversion of atrial fibrillation, wherein the control unit is configured such that a defined phase of CCM therapy always precedes a cardioversion attempt in response to atrial fibrillation in order to improve a success of cardioversion.
6. The cardiac stimulator according to any one of claims 1 to 3, characterised in that the cardiac stimulator additionally comprises a further sensor, which delivers an output signal that reflects the activity, metabolic demand, and/or ventricular potential, or which is a renal function sensor, pulmonary function sensor, cardiac function sensor, electrolyte sensor, neurosensor/vagus nerve/sympathetic nervous system, adverse event sensor, worsening heart failure sensor, sleep apnoea sensor, ischemia sensor or infarct sensor, and is connected to the control unit, wherein the control unit is configured to evaluate the output signal of said sensor and to use this to control the contractility modulation.

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